Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients

被引:87
作者
Marofi, Faroogh [1 ]
Rahman, Heshu Sulaiman [2 ,3 ]
Al-Obaidi, Zaid Mahdi Jaber [4 ,5 ]
Jalil, Abduladheem Turki [6 ]
Abdelbasset, Walid Kamal [7 ,8 ]
Suksatan, Wanich [9 ]
Dorofeev, Aleksei Evgenievich [10 ]
Shomali, Navid [1 ]
Chartrand, Max Stanley [11 ]
Pathak, Yashwant [12 ,13 ]
Hassanzadeh, Ali [1 ]
Baradaran, Behzad [1 ]
Ahmadi, Majid [14 ]
Saeedi, Hossein [1 ]
Tahmasebi, Safa [15 ]
Jarahian, Mostafa [16 ]
机构
[1] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran
[2] Univ Sulaimani, Coll Med, Sulaimaniyah, Iraq
[3] Komar Univ Sci & Technol, Dept Med Lab Sci, Chaq Chaq Qularaise, Sulaimaniyah, Iraq
[4] Univ Alkafeel, Coll Pharm, Dept Pharmaceut Chem, Najaf 54001, Iraq
[5] Univ Kerbala, Coll Med, Dept Chem & Biochem, Karbala 56001, Iraq
[6] Yanka Kupala State Univ Grodno, Fac Biol & Ecol, Grodno, BELARUS
[7] Prince Sattam Bin Abdulaziz Univ, Coll Appl Med Sci, Dept Hlth & Rehabil Sci, Al Kharj, Saudi Arabia
[8] Cairo Univ, Kasr Al Aini Hosp, Dept Phys Therapy, Giza, Egypt
[9] Chulabhorn Royal Acad, HRH Princess Chulabhorn Coll Med Sci, Fac Nursing, Bangkok 10210, Thailand
[10] Sechenov First Moscow State Med Univ, Moscow, Russia
[11] DigiCare Behav Res, Casa Grande, AZ USA
[12] Univ S Florida, Taneja Coll Pharm, Tampa, FL 33620 USA
[13] Airlangga Univ, Fac Pharm, Dept Pharmaceut, Surabaya, Indonesia
[14] Tabriz Univ Med Sci, Stem Cell Res Ctr, Tabriz, Iran
[15] Univ Tehran Med Sci, Sch Publ Hlth, Dept Immunol, Tehran, Iran
[16] German Canc Res Ctr, Toxicol & Chemotherapy, 2,Floor 4 Unit G401, D-69120 Heidelberg, Germany
关键词
Acute myeloid leukemia; Adoptive cell therapy; Chimeric antigen receptor T cells; Hematological malignancy; Target antigen; ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; CHIMERIC ANTIGEN RECEPTORS; PHASE-I; ADOPTIVE IMMUNOTHERAPY; GEMTUZUMAB OZOGAMICIN; ANTITUMOR EFFICACY; NKG2D RECEPTOR; SUICIDE-GENE; BONE-MARROW;
D O I
10.1186/s13287-021-02420-8
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.
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